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particularly for long delays. However, in cases in which the STEMI
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particularly for long delays. However, in cases in which the STEMI diagnosis is not clear, delaying P2Y 12 inhibitor loading until the anat- omy is known should be considered. The preferred P2Y 12 inhibitors are prasugrel [60 mg loading dose and 10 mg maintenance dose once daily per os (p.o.)] or ticagrelor (180 mg p.o. loading dose and 90 mg maintenance dose twice daily). These drugs have a more rapid onset of action, greater potency, and are superior to clopidogrel in clinical outcomes. 186 , 187 Prasugrel is contraindicated in patients with previous stroke/transient ischaemic attack, and its use is generally not recommended in patients aged 75 years or in patients with lower body weight (<60 kg) as it was not associated with net clinical benefit in these subsets. In case prasu- grel is used in these patients, a reduced dose (5 mg) 188 is recom- mended. Ticagrelor may cause transient dyspnoea at the onset of therapy, which is not associated with morphological or functional lung abnormalities, and which rarely leads to permanent discontinua- tion. 189 Neither prasugrel nor ticagrelor should be used in patients with a previous haemorrhagic stroke, in patients on oral anticoagu- lants, or in patients with moderate-to-severe liver disease. When neither of these agents is available (or if they are contraindi- cated), clopidogrel 600 mg p.o. should be given instead. 190 Clopidogrel has not been evaluated against placebo in any large out- comes studies in the setting of primary PCI, but a higher regimen of a 600 mg loading dose/150 mg maintenance dose in the first week was superior to the 300/75 mg regimen in the subset of patients under- going PCI in the Clopidogrel and aspirin Optimal Dose usage to reduce recurrent events–Seventh organization to assess strategies in ischaemic syndromes (CURRENT-OASIS 7) trial, 190 and use of high clopidogrel loading doses has been demonstrated to achieve more rapid inhibition of the adenosine diphosphate receptor. All P2Y 12 inhibitors should be used with caution in patients at high risk of bleed- ing or with significant anaemia. Cangrelor is a potent i.v. reversible P2Y 12 inhibitor with a rapid onset and offset of action. It has been assessed in three random- ized controlled trials enrolling patients with PCI for stable angina or ACS against clopidogrel loading or placebo. 191 – 193 A pooled analysis of these three trials showed that cangrelor reduced peri- procedural ischaemic complications at the expense of an increased risk of bleeding. 194 The fact that no potent P2Y 12 inhibitors (prasu- grel or ticagrelor) were used in patients with an ACS, and only about 18% of the enrolled patients presented with STEMI, 193 limits the applicability of the results to current practice of management of STEMI patients. Nevertheless, cangrelor may be considered in patients not pre-treated with oral P2Y 12 receptor inhibitors at the time of PCI or in those who are considered unable to absorb oral agents. The pre-hospital routine upstream use of glycoprotein (GP) IIb/IIIa inhibitors before primary PCI has not been demonstrated to offer a benefit and increases bleeding risk compared with routine use in the catheterization laboratory. 195 , 196 Procedural use of abciximab plus unfractionated heparin (UFH) showed no benefit compared to biva- lirudin. 197 Using GP IIb/IIIa inhibitors as bailout therapy in the event of angiographic evidence of a large thrombus, slow- or no-reflow, and other thrombotic complications is reasonable, although this strategy has not been tested in a randomized trial. Overall, there is no evi- dence to recommend the routine use of GP IIb/IIIa inhibitors for pri- mary PCI. The intracoronary administration of GP IIb/IIIa inhibitors is not superior to its i.v. use. 198 5.2.2.2 Anticoagulation Anticoagulant options for primary PCI include UFH, enoxaparin, and bivalirudin. Use of fondaparinux in the context of primary PCI was associated with potential harm in the Organization for the Assessment of Strategies for Ischemic Syndromes 6 (OASIS 6) trial and is not recommended. 199 There has been no placebo-controlled trial evaluating UFH in pri- mary PCI, but there is a large body of experience with this agent. 136 ESC Guidelines Downloaded from https://academic.oup.com/eurheartj/article-abstract/39/2/119/4095042 by E-Library Insel user on 07 February 2018 Dosage should follow standard recommendations for PCI (i.e. initial bolus 70–100 U/kg). There are no robust data recommending the use of activated clotting time to tailor dose or monitor UFH, and if activated clotting time is used, it should not delay recanalization of the IRA. An i.v. bolus of enoxaparin 0.5 mg/kg was compared with UFH in the randomized open-label Acute myocardial infarction Treated with primary angioplasty and inTravenous enOxaparin or unfractionated heparin to Lower ischaemic and bleeding events at short- and Long-term follow-up (ATOLL) trial, including 910 STEMI patients. 200 The primary composite endpoint of 30 day death, MI, procedural failure, or major bleeding was not significantly reduced by enoxaparin (17% relative risk reduction, P = 0.063), but there was a reduction in the composite main secondary endpoint of death, recur- rent MI or ACS, or urgent revascularization. Importantly, there was no evidence of increased bleeding following the use of enoxaparin over UFH. 200 In the per-protocol analysis of the ATOLL trial (87% of the study population), i.v. enoxaparin was superior to UFH in reduc- ing the primary endpoint, ischaemic endpoints, mortality, and major bleeding. 201 In a meta-analysis of 23 PCI trials (30 966 patients, 33% primary PCI), enoxaparin was associated with a significant reduction in death compared to UHF. This effect was particularly significant in the primary PCI context and was associated with a reduction in major bleeding. 202 Based on these considerations, enoxaparin should be considered in STEMI. Five dedicated randomized controlled trials have compared bivalir- udin with UFH with or without planned use of GP IIb/IIIa inhibitors in patients with STEMI. 197 , 203 – 207 A meta-analysis of these trials showed no mortality advantage with bivalirudin and a reduction in the risk of major bleeding, but at the cost of an increased risk of acute stent thrombosis. 208 In the recent MATRIX trial including 7213 ACS patients (56% with STEMI), bivalirudin did not reduce the incidence of the primary endpoint (composite of death, MI, or stroke) com- pared to UFH. Bivalirudin was associated with lower total and cardio- vascular mortality, lower bleeding, and more definite stent thrombosis. 209 The recently published STEMI subanalysis confirmed a lack of statistical interaction between the type of ACS and out- comes within the study. 210 The MATRIX trial showed that prolonging bivalirudin infusion after PCI did not improve the outcomes com- pared with bivalirudin infusion confined to the duration of PCI. 209 However, a post hoc analysis suggested that prolonging bivalirudin with a full-PCI dose after PCI was associated with the lowest risk of ischaemic and bleeding events, which is in accordance with the cur- rent label of the drug. 209 Based on these data, bivalirudin should be considered in STEMI, especially in patients at high bleeding risk. 197 , 211 , 212 Bivalirudin is recommended for patients with heparin- induced thrombocytopenia. Routine post-procedural anticoagulant therapy is not indicated after primary PCI, except when there is a separate indication for either full-dose anticoagulation [due, for instance, to atrial fibrillation (AF), mechanical valves, or LV thrombus) 2 or prophylactic doses for the prevention of venous thromboembolism in patients requiring prolonged bed rest. Periprocedural and post-procedural antithrombotic therapy a in patients undergoing primary percutaneous coronary intervention Recommendations Class b Level c Antiplatelet therapy A potent P2Y 12 inhibitor (prasugrel or tica- grelor), or clopidogrel if these are not avail- able or are contraindicated, is recommended before (or at latest at the time of) PCI and maintained over 12 months, unless there are contraindica- tions such as excessive risk of bleeding. 186 , 187 I A Aspirin (oral or i.v. if unable to swallow) is recommended as soon as possible for all patients without contraindications. 213 , 214 I B GP IIb/IIIa inhibitors should be considered for bailout if there is evidence of no-reflow or a thrombotic complication. IIa C Cangrelor may be considered in patients who have not received P2Y 12 receptor inhibitors. 192 – 194 IIb A Anticoagulant therapy Anticoagulation is recommended for all patients in addition to antiplatelet therapy during primary PCI. I C Routine use of UFH is recommended. I C In patients with heparin-induced thrombo- cytopenia, bivalirudin is recommended as the anticoagulant agent during primary PCI. I C Routine use of enoxaparin i.v. should be considered. 200 – 202 IIa A Routine use of bivalirudin should be considered. 209 , 215 IIa A Fondaparinux is not recommended for pri- mary PCI. 199 III B GP = glycoprotein; i.v. = intravenous; PCI = percutaneous coronary intervention; UFH = unfractionated heparin. a Dose regimens are specified in Table 6 . b Class of recommendation. c Level of evidence. ESC Guidelines 137 Downloaded from https://academic.oup.com/eurheartj/article-abstract/39/2/119/4095042 by E-Library Insel user on 07 February 2018 .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. . 5.2.2.3 Therapies to reduce infarct size and microvascular obstruction Final infarct size and MVO are major independent predictors of long-term mortality and heart failure in survivors of STEMI. 216 , 217 MVO is defined as inadequate myocardial perfusion after success- ful mechanical opening of the IRA, and is caused by several fac- tors. 218 MVO is diagnosed immediately after PCI when post- procedural angiographic TIMI flow is < 3, or in the case of a TIMI flow of 3 when myocardial blush grade is 0 or 1, or when ST reso- lution within 60–90 min of the procedure is < 70%. Other non- invasive techniques to diagnose MVO are late gadolinium enhancement (LGE) CMR (the current state of the art for MVO identification and quantification), contrast echocardiography, single-photon emission computed tomography (SPECT), and posi- tron emission tomography (PET). 218 Different strategies, such as coronary post-conditioning, remote ischaemic conditioning, early i.v. metoprolol, GP IIb/IIIa inhibitors, drugs targeting mitochondrial integrity or nitric oxide pathways, adenosine, glucose modulators, hypothermia, and others, have been shown to be beneficial in pre- clinical and small-scale clinical trials, 217 , 219 but still there is no ther- apy aimed at reducing ischaemia/reperfusion injury (MI size) that is clearly associated with improved clinical outcomes. The reduction of ischaemia/reperfusion injury in general, and MVO in particular, remains an unmet need to further improve long-term ventricular function in STEMI. 5.3 Fibrinolysis and pharmacoinvasive strategy 5.3.1 Benefit and indication of fibrinolysis Fibrinolytic therapy is an important reperfusion strategy in settings where primary PCI cannot be offered in a timely manner, and pre- vents 30 early deaths per 1000 patients treated within 6 h after symptom onset. 220 The largest absolute benefit is seen among patients at highest risk, including the elderly, and when treatment is offered <2 h after symptom onset. 138 , 221 Fibrinolytic therapy is recommended within 12 h of symptom onset if primary PCI can- not be performed within 120 min from STEMI diagnosis (see Figure 3 ) and there are no contraindications. The later the patient presents (particularly after 3 h), 98 , 120 , 121 the more consideration should be given to transfer for primary PCI (as opposed to admin- istering fibrinolytic therapy) because the efficacy and clinical bene- fit of fibrinolysis decrease as the time from symptom onset increases. 120 In the presence of contraindications for fibrinolytic treatment, it is important to weigh the potentially life-saving effect of fibrinolysis against potentially life-threatening side effects, taking into account alternative treatment options such as delayed primary PCI. Table 6 Doses of antiplatelet and anticoagulant cotherapies in patients undergoing primary percutane- ous coronary intervention or not reperfused b.i.d. = twice a day; GP = glycoprotein; i.v. = intravenous; IU = international units; PCI = percutaneous coronary intervention; UFH = unfractionated heparin. 138 ESC Guidelines Downloaded from https://academic.oup.com/eurheartj/article-abstract/39/2/119/4095042 by E-Library Insel user on 07 February 2018 .. .. .. .. .. .. .. .. .. .. .. .. Doses of fibrinolytic agents and antithrombotic co-therapies are listed in Table 7 . 5.3.2 Pre-hospital fibrinolysis In a meta-analysis of six randomized trials (n = 6434), pre-hospital fibrinolysis reduced early mortality by 17% compared with in-hospital fibrinolysis, 123 tải về 4.91 Mb. Chia sẻ với bạn bè của bạn:
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